Cyclic 3',5'-adenosine monophosphate and bronchial tone

Abstract

The present studies demonstrate that adenylate cyclase and cyclic 3',5'-adenosine monophosphate (cAMP)-phosphodiesterase activities in dog bronchus are comparable to those found in other smooth muscle preparations. Catecholamines, in the order isoproterenol greater than epinephrine greater than norepinephrine, increase the rate of cAMP formation. This effect can be competitively inhibited by propranolol and potentiated by a cAMP-phosphodiesterase inhibitor. The kinetic study of bronchial cAMP-phosphodiesterase showed two different rates of cAMP hydrolysis, with apparent Km values of 1.4 and 48.0 muM. The high affinity cAMP-phosphodiesterase was inhibited competitively by theophylline and papaverine, the latter being about 20 times more potent than the former. The potency of each compound to inhibit the enzyme and to relax the bronchial strip was comparable. These results, the similar order of potency of the catecholamines to relax the bronchus and to increase the rate of cAMP formation, the competitive inhibition of both effects by propranolol, and the relaxing effect of dibutyryl cAMP on bronchial strip, are compatible with the assumption that the cAMP system is one of the biochemical mechanisms mediating bronchial smooth muscle relaxation.